title: Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing.
abstract: The downstream consequences of inflammation in the adult mammalian heart are formation of a non-functional scar, pathological remodelling and heart failure. In zebrafish, hydrogen peroxide released from a wound is the initial instructive chemotactic cue for the infiltration of inflammatory cells, however, the identity of a subsequent resolution signal(s), to attenuate chronic inflammation, remains unknown. Here we reveal that thymosin β4-sulfoxide lies downstream of hydrogen peroxide in the wounded fish and triggers depletion of inflammatory macrophages at the injury site. This function is conserved in the mouse and observed after cardiac injury, where it promotes wound healing and reduced scarring. In human T-cell/CD14+ monocyte co-cultures, thymosin β4-sulfoxide inhibits interferon-γ, and increases monocyte dispersal and cell death, likely by stimulating superoxide production. Thus, thymosin β4-sulfoxide is a putative target for therapeutic modulation of the immune response, resolution of fibrosis and cardiac repair.
authors.affiliation: Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, South Parks Road, Oxford OX1 3PT, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Evans
authors.forename: Nicola
authors.initials: N
authors.lastname: Smart
authors.forename: Karina N
authors.initials: KN
authors.lastname: Dubé
authors.forename: Sveva
authors.initials: S
authors.lastname: Bollini
authors.forename: James E
authors.initials: JE
authors.lastname: Clark
authors.forename: Hayley G
authors.initials: HG
authors.lastname: Evans
authors.forename: Leonie S
authors.initials: LS
authors.lastname: Taams
authors.forename: Rebecca
authors.initials: R
authors.lastname: Richardson
authors.forename: Mathieu
authors.initials: M
authors.lastname: Lévesque
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Kevin
authors.initials: K
authors.lastname: Mills
authors.forename: Johannes
authors.initials: J
authors.lastname: Riegler
authors.forename: Anthony N
authors.initials: AN
authors.lastname: Price
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lythgoe
authors.forename: Paul R
authors.initials: PR
authors.lastname: Riley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology*; D007962:Leukocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013947:Thymosin / Q000737:chemistry / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*; D015027:Zebrafish; D000099201:Thymosin beta(4)
chemical_list: D006861:Hydrogen Peroxide; D017382:Reactive Oxygen Species; D013947:Thymosin; D000099201:Thymosin beta(4); C094615:thymosin beta(4) sulfoxide